Welbeck went down awkwardly after challenging for a header in the box after 25 minutes and needed immediate attention.
The medics came onto the pitch and tended to the Arsenal forward for about five minutes as his team-mates looked on distraught.
He was given oxygen before being carried off on a stretcher and replaced by Pierre-Emerick Aubameyang.
BT Sport commentator Ian Darke said: “Obviously the medical team here will give him as much time as needed.
READ MORE: ARSENAL PLAYERS DISTRAUGHT AS WELBECK IS CARRIED OFF
“And the look on the players’ faces is worrying isn’t it. Look at that.
“I have to tell you there is some concern here and you can see it on those faces.”
Welbeck will almost certainly be out of the England squad for the games against the USA and Croatia after receiving his latest call up earlier today.
The 27-year-old has a horror history with injuries and this looks set to be another bad one.
Danny Welbeck injury: Arsenal ace Welbeck was carried off during the Europa League clash
Danny Welbeck injury: Welbeck was taken off during the first half
Danny Welbeck injury: Welbeck points to his ankle while being tended to by the medics
Danny Welbeck injury: Welbeck was tended to by medics on the pitch
Welbeck, who is out of contract in the summer, has scored four goals in his last 10 games including one in the return match with Sporting.
He has been a regular in the Europa League under Unai Emery but has only started once in the Premier League this season.
“Matteo Guendouzi among those looking on,” Darke continued. “Horrible to witness, always.
“The physios have done their best and all you can do in this situation is wish the very best to Danny Welbeck for what is clearly a serious injury.”
Danny Welbeck injury: Welbeck is carried off on a stretcher
Danny Welbeck injury: Welbeck is taken off during the first event
Danny Welbeck injury: Danny Welbeck is carried off the pitch with a serious injury
Darke added: “Sometimes when there’s a bad injury when the game resumes you often see for a while not many tackles going in. I can think of a few instances of that that we’ve witnessed down the years.”
Stewart Robson said: “Certainly a player on this field in that situation, Aaron Ramsey at Stoke City.”
Arsenal tweeted: “After a lengthy delay, it’s going to be a sad end to tonight’s game for @DannyWelbeck…
“Welbz is substituted to the sound of Emirates Stadium chanting his name
“We’re all hoping for the best for you, Danny.”
Former Arsenal defender Martin Keown admits these kind of injuries can shock the other players on the pitch.
“When you see that on a pitch, and I have seen that a couple of times, it’s always a bit shocking,” he said on BT Sport.
“Maybe it’s a problem with the ankle, we don’t want to speculate, is it a dislocation?
“He was getting gas and air there at some point.
“You see the players and it reflects on their faces really.
“I think they realise, look at that, something serious has happened.
“We wish him well, he is probably the nicest man I’ve met in football.
“When you know Danny he’s a great guy, heart and soul of the football club.
“He’s been desperately unlucky with injuries, that’s for sure.”
Mesut Ozil tweeted: “Oh no … get well soon Danny.”
Arsenal are hoping to seal qualification to the Europa League knockout stages with victory tonight but a draw may be enough depending on results.
Danny Welbeck injury: How it happened
Knee and cartilage injuries had robbed him of 70 games between May 2015 and January 2017, and all those injury nightmares were revisited in what looked at first an innocuous enough challenge for the ball in the 26th minute.
Welbeck jumped alongside former Liverpool defender Sebastian Coates near the penalty spot and after squeezing a tame header towards goal appeared to land badly, twisting his right foot completely back on itself.
The stretcher was quickly called for and there was marked discomfort etched on the face of team-mate Matteo Guendouzi as he watched on while the seven-man medical team administered what appeared to be oxygen and pain-killers to the stricken 27-year-old as he was helped gingerly off the field with his right foot heavily braced.